Relationship between podoplanin-expressing cancer-associated fibroblasts and the immune microenvironment of early lung squamous cell carcinoma

Suzuki, Jun; Aokage, Keiju; Neri, Shinya; Sakai, Takashi; Hashimoto, Hiroko; Su, Yinghan; Yamazaki, Shota; Nakamura, Hiroshi; Tane, Kenta; Miyoshi, Tomohiro; Sugano, Masato; Kojima, Masaru; Fujii, Satoshi; Kuwata, Takeshi; Ochiai, Atsushi; Tsuboi, Masahiro; Ishii, Genichiro

doi:10.1016/j.lungcan.2020.12.020

Cited by 59 publications

(53 citation statements)

References 47 publications

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“…Tumor microenvironment, especially tumor immune and stromal microenvironment, constitute a vital element of tumor tissue. Increasing evidence has revealed their clinicopathological significance in predicting outcomes and therapeutic efficacy ( Greten and Grivennikov, 2019 ; Vitale et al, 2019 ; Suzuki et al, 2021 ). TAMs and CAFs in TME always accelerate tumor progression ( Akins et al, 2020 ; Liu et al, 2021 ; Shan et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…TGFB1, mainly secreted by TAMs and CAFs in TME, play an irreplaceable role in inducing immunosuppressive microenvironment. Immunosuppressive genes, such as IL10, IL10RB, LGALS9, and LAG3, were observed to be co-overexpressed with TGFB1 in tumor tissues and predicted poor survival of tumor patients, indicating a potential mechanism by which CCDC137 regulates macrophage polarization, CAFs formation and correlates with several immunosuppressive genes ( Kadowaki et al, 2016 ; Fan et al, 2020 ; Suzuki et al, 2021 ; Wang et al, 2021 ). In addition, the high expression of CCDC137 indicates the immunosuppression status in LGG and UVM, providing a potential drug target for tumor therapy.…”

Section: Discussionmentioning

confidence: 99%

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CCDC137 Is a Prognostic Biomarker and Correlates With Immunosuppressive Tumor Microenvironment Based on Pan-Cancer Analysis

Guo

et al. 2021

Front. Mol. Biosci.

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BackgroundThe coiled-coil domain containing (CCDC) family proteins have important biological functions in various diseases. However, the coiled-coil domain containing 137 (CCDC137) was rarely studied. We aim to investigate the role of CCDC137 in pan-cancer.MethodsCCDC137 expression was evaluated in RNA sequence expression profilers of pan-cancer and normal tissues from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database. The influence of CCDC137 on the prognosis of tumor patients was analyzed using clinical survival data from TCGA. Function and pathway enrichment analysis was performed to explore the role of CCDC137 using the R package “clusterProfiler.” We further analyzed the correlation of immune cell infiltration score of TCGA samples and CCDC137 expression using TIMER2 online database.ResultsCCDC137 was over-expressed and associated with worse survival status in various tumor types. CCDC137 expression was positively correlated with tumor associated macrophages (TAMs) and cancer associated fibroblasts (CAFs) in Lower Grade Glioma (LGG) and Uveal Melanoma (UVM). In addition, high CCDC137 expression was positively correlated with most immunosuppressive genes, including TGFB1, PD-L1, and IL10RB in LGG and UVM.ConclusionsOur study identified CCDC137 as an oncogene and predictor of worse survival in most tumor types. High CCDC137 may contribute to elevated infiltration of TAMs and CAFs and be associated with tumor immunosuppressive status.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CCDC137 Is a Prognostic Biomarker and Correlates With Immunosuppressive Tumor Microenvironment Based on Pan-Cancer Analysis

Guo

et al. 2021

Front. Mol. Biosci.

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“… 52 Suzuki et al showed that podoplanin + CAFs exhibited higher expression of TGFβ1 and were associated with CD204 + tumor-associated macrophages infiltration in stage-I lung squamous cell carcinoma. 13 Dai et al showed that the upregulation of podoplanin in CAFs increase tumor migration, proliferation, metastasis and malignancy. 53 Neri et al demonstrated that podoplanin + CAFs displayed a higher RhoA activity and treatment with a ROCK inhibitor canceled the increased invasion ability of podoplanin + CAFs and subsequently decreased the invasion and metastasis ability of tumor cells.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Value of Podoplanin in Various Tumors

Wang

Carvalho

Wang

et al. 2021

Technol Cancer Res Treat

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Background: The prognostic significance of podoplanin (PDPN) in tumor cells for cancer patients’ survival remains controversial. Therefore, we performed this meta-analysis to clarify the relationship between the podoplanin-positive tumor cells and cancer prognosis. Method: Eligible studies were identified by searching the Pubmed and EBSCO online databases up to August 2019. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to evaluate the correlation between podoplanin expression and overall survival (OS) and/or disease-free survival (DFS) and odds ratios (ORs) with 95% CIs severed as the summarized statistics for clinicopathological characteristic. Results: A total of 2155 patients from 21 eligible studies were included. The results revealed that high expression of podoplanin was associated with a poor survival rate in cancer patients. Further subgroup analysis stratified by tumor type showed that podoplanin-positive tumor cell infiltration had a negative prognostic effect associated with survival in esophageal cancer and oropharyngeal cancer. In addition, high expression of these cells was significantly associated with N stage, T stage, TNM stage and vascular invasion. Conclusion: Our study suggests the over-expression of podoplanin might be a significant prognostic indicator for patients with esophageal and oropharyngeal cancer.

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“…CAFs can also promote skin tumor development by maintaining monocyte chemotactic protein-1 (MCP-1) mediated macrophage infiltration and chronic inflammation (235). Podoplanin + CAFs were recently reported to be associated with CD204 + TAM infiltration in lung squamous cell carcinoma (236). Moreover, podoplanin + CAFs were also found to be associated with monocyte recruitment and differentiation into CD204 + TAMs in lung adenocarcinoma (237).…”

Section: The Interplay Between Cafs and Tamsmentioning

confidence: 99%

CAFs Interacting With TAMs in Tumor Microenvironment to Enhance Tumorigenesis and Immune Evasion

Günaydın

2021

Front. Oncol.

103

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Cancer associated fibroblasts (CAFs) and tumor associated macrophages (TAMs) are among the most important and abundant players of the tumor microenvironment. CAFs as well as TAMs are known to play pivotal supportive roles in tumor growth and progression. The number of CAF or TAM cells is mostly correlated with poor prognosis. Both CAFs and TAMs are in a reciprocal communication with the tumor cells in the tumor milieu. In addition to such interactions, CAFs and TAMs are also involved in a dynamic and reciprocal interrelationship with each other. Both CAFs and TAMs are capable of altering each other’s functions. Here, the current understanding of the distinct mechanisms about the complex interplay between CAFs and TAMs are summarized. In addition, the consequences of such a mutual relationship especially for tumor progression and tumor immune evasion are highlighted, focusing on the synergistic pleiotropic effects. CAFs and TAMs are crucial components of the tumor microenvironment; thus, they may prove to be potential therapeutic targets. A better understanding of the tri-directional interactions of CAFs, TAMs and cancer cells in terms of tumor progression will pave the way for the identification of novel theranostic cues in order to better target the crucial mechanisms of carcinogenesis.

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Relationship between podoplanin-expressing cancer-associated fibroblasts and the immune microenvironment of early lung squamous cell carcinoma

Cited by 59 publications

References 47 publications

CCDC137 Is a Prognostic Biomarker and Correlates With Immunosuppressive Tumor Microenvironment Based on Pan-Cancer Analysis

CCDC137 Is a Prognostic Biomarker and Correlates With Immunosuppressive Tumor Microenvironment Based on Pan-Cancer Analysis

Prognostic Value of Podoplanin in Various Tumors

CAFs Interacting With TAMs in Tumor Microenvironment to Enhance Tumorigenesis and Immune Evasion

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